by Milind Mukkamala, Raina Singhal, Priya Lokasundaram, The GTF Group

Introduction

We are the members of the Global Thrombosis Forum (GTF, www.gtfonline.net) is a nonprofit organization that is an affiliate of North American Thrombosis Forum (NATF, www.natfonlione.org). GTF tries to spread awareness on the deadly condition of thrombosis. We achieve this by arranging booths at various events, explaining the risks and preventive measures about thrombosis, preparing publications or posters, and networking, all done by its youth and adult members.

Recently, a first case of deep vein thrombosis (DVT or simply put, a blood clot) was discovered in an astronaut in space. Fortunately, the doctors were able to treat the clot and the astronaut is doing well.

We researched this event, the challenges that were with the team, and the efforts by physicians, and the astronauts to combat the clot to bring it to a resolution.

How did it get started?

It is a very interesting story. A phone call came to Dr. Stephan Moll, a World renowned expert in diseases of blood (also called a hematologist) and a long-time NASA enthusiast, at his residence. His wife, who answered the call, said, “Stephan, there is a phone call for you from space.” NASA thus had reached out to Dr. Moll, who is considered an expert in the field of hematology. Dr. Moll was astonished that NASA was on the phone, and was told that NASA wanted to consult with him about a blood clot in the neck vein of an astronaut. Dr. Moll, being a very helpful physician, agreed to help NASA immediately.

A blood clot in the jugular vein (neck vein) of the astronaut?

As part of the research protocol in space, the astronauts routinely perform ultrasound examinations on themselves. The astronaut found the blood clot in the jugular vein in the neck during one of those examinations.

Any person involved with DVT should normally present headache or worsening of the facial plethora. Surprisingly, the astronaut was completely asymptomatic. In fact, there was never any impression of anything being wrong.

Furthermore, in a few cases, the thrombus could have a family history.  In this case, the astronaut had no personal or family history of venous thromboembolism, (VTE).

All other major veins in the astronaut were found to be normal! It is interesting that cases like these with internal jugular venous thrombosis on Earth are typically associated with cancer, a central venous catheter, or ovarian hyperstimulation. Random cases of jugular vein DVT are very uncommon.

DVT, what next?

Not having any symptoms while having the clot sounds quite scary. Since this was the first incident in space, NASA did not have any established treatment plan for this condition in zero gravity, even scarier. It is here that NASA approached Dr. Moll for consultation.

Dr. Moll did not have to go to space (although he told us that he was ready to fly to space) to see the astronaut, and he spoke with through emails and phone calls. The treatment started shortly after the diagnosis.

Now, under the normal circumstances, the protocol would be to treat a patient with DVT with anticoagulants, more commonly known as blood thinners, 3 months in advance. The purpose of this exercise is to prevent the clot from getting bigger and to lessen the harm it could cause if it moved to a different part of the body such as the lungs. But in this case this option was not applicable, because the astronaut did not have a history of DVT.

Dr. Moll and NASA physicians therefore decided that anticoagulants (also called blood thinners) would be the best course of treatment. Luckily, the international space station (ISS) had a small supply of the blood thinner enoxaparin.

Risks of the use of anticoagulants in space

Although the primary goal was to manage the blood clot, there were risks and challenges associated with the treatment plan with the use of anticoagulants.

First of all, if an injury occurs, it could cause internal bleeding that may be difficult to stop.

Second, if bleeding occurred, emergency medical attention would not be feasible since there is no ER in the space.                                                                             Third, there were no drugs on board to antagonize the effects of the anticoagulant.

The team, therefore, had to weigh the options at hand very carefully.

Challenges

As if the risks were not enough, there were several challenges that the team had to face and work through.

• The International Space Station (ISS) keeps only a small supply of medicines on board, and there was a limited amount of the anticoagulant enoxaparin (Lovenox®) available.
• Moll advised NASA on the dosage of enoxaparin to treat DVT, until a new shipment of drugs was sent to the ISS.
• Because of this, there was an acute need for clinical decision making for the treatment. They performed a radiologist-guided telemedicine to locate the blood clot and manage the progress before making any critical decisions.
• They had no anticoagulation-reversal agent to enoxaparin available on board.

How were the challenges handled?

1. Supplies of enoxaparin, protamine and prothrombin complex concentrate as reversal agents to enoxaparin were sent to the space station.
2. Since the physicians were more familiar with apixaban, one of the Direct Oral AntiCoagulants (also referred to as DOAC’s) than other anticoagulants, and new data from the research studies showed that apixaban may lead to less clinically relevant bleeding than other DOAC’s, the team chose to use apixaban to follow the treatment with enoxaparin.
3. To minimize this risk of bleeding, the dosage of enoxaparin was reduced from 1.5 mg/kg to 1 mg/kg after 33 days of therapy.
4. Oral apixaban, once available in the ISS, replaced enoxaparin after its use for 42 days.
5. The initial dose of apixaban 5 mg given twice a day was reduced to 2.5 mg twice a day.
6. Four days prior to the astronaut’s journey home to the Earth, the astronaut was asked to stop taking apixaban. Why? Dr. Moll and his NASA counterparts made this decision because of how physically demanding and potentially dangerous the re-entry process can be for astronauts. They did not want an injury to be exacerbated by the use of anticoagulants.

Safe landing on the Earth

The astronaut landed safely on earth. Upon landing, a spontaneous blood flow and flattening of the residual thrombus was observed. Regular sonographic surveillance (ultrasound examinations) showed progressive volume reduction of the thrombus. So the treatment was working !!

Follow-up

All patients who suffer from DVT need a follow-up. Follow-up examinations revealed a small residual thrombus 24 hours after landing. No thrombus was observed 10 days after landing. This led the team to believe that further anticoagulation was unnecessary. Since there was no more blood clot, no more treatment needed. At this time, the team members discontinued apixaban. During a follow-up 6 months after the return to Earth, the astronaut continued to be asymptomatic.

Gaps in our understanding of the case

Since this was the very first case of thrombosis in space, it is to be expected that there would be some gaps in our understanding of circulatory and hemostatic physiology.

1. Although overcapacity of blood in the veins of the brain is a known effect of spaceflight, the resultant changes in flow, local whole-blood viscosity, and prothrombotic risk need further exploration.
2. An active astronaut surveillance and experimental models are critical.
3. A lot more work also needs to be done in terms of the absorption, distribution, metabolism, and excretion (ADME) of drugs in space.

How did we collect so much information?

Well, this has an interesting background.  None of us knew Dr. Moll. However, Dr. Laddu happened to meet with Dr. Moll in Atlanta in person on January 25, 2020, when there was no COVID-19 at that time, after knowing about Dr. Moll’s success story that he had just published in the World Renowned New England Journal of Medicine (January 2020).  Dr. Laddu then introduced Dr. Moll to the young members of GTF, and we interviewed Dr. Moll. It was during this interview that Dr. Moll told us all the details.

Summary and Conclusions

1. We conducted research on the first case of thrombosis in space in an astronaut, after interviewing Dr. Moll.
2. There were several challenges in Space that the NASA scientists had to face.
3. The astronaut was initially given enoxaparin and afterwards apixaban, resulting in a complete resolution of the blood clot.
4. This was the first incidence of DVT that took place in zero gravity.
5. A lot more work needs to be done in terms of the absorption, distribution, metabolism, and excretion (ADME) of drugs in space.

Acknowledgements

1. The authors would like to thank Dr. Stephan Moll for providing significant information from his research and personal experience.
2. Additionally, we want to express our gratitude towards Dr. Atul Laddu and Ms. Ujjwala Juvekar for coaching us and our respective parents for their support along with the GTF team.

About the Author:

Mr. Milind Mukkamala is a 10th grader at the Johns Creek High School and wants to follow a career in Economics and Business Development

Ms. Priya Lokasundaram is a nursing student at the Mercer University Baptist College of Nursing. Her passion is to mentor young children. 

Ms. Raina Singhal is a 10th grader at the Alpharetta High School, Alpharetta, GA.  She wants to pursue a career as a General Surgeon.